Issues

In Greek mythology, Sisyphus has tricked death twice and, as a punishment, has been doomed to push a heavy rock uphill, only to run out of steam near the top, where the rock escapes his grip and rolls back down. This cycle, reminiscent of a transient response to therapy followed by a relapse, is futile unless the man would eventually come up with a clever trick to outsmart this destiny. In this issue, Meermeier and colleagues show that in animals with high tumor burden, responses to bispecific T-cell engager (BiTE) antibody therapy of myeloma are limited by exhaustion of T cells. The outcome of this uphill battle can be overturned by the addition of cyclophosphamide, which reduces the tumor load and prevents T-cell exhaustion when combined with BiTE therapy, leading to tumor clearance and long-term protective myeloma-specific immunity. For details, please see the article on page 354 and the accompanying commentary by Louvet, Nadeem, and Smith on page 297.